Role of bile bacteria in gallbladder carcinoma

Abstract

Background/aims: Long standing calculus disease has been observed to be a risk factor for gallbladder carcinoma. However it is possible that calculi may be incriminated by some means other than just chronic irritation. Calculi may induce an element of stasis, promoting chronic infection leading to increased turnover of primary bile acids to secondary bile acids, which are known tumor promoters and initiators. This study aimed to find the prevalence of biliary microflora in gallbladder carcinoma and association of gallbladder carcinoma with chronic bacterial infection and bile acid profile.

Methodology: Bile culture was done in 390 patients divided into 3 groups--gallbladder carcinoma 65 (17%), cholelithiasis 125 (32%) and control group 200 (51%). Serum samples were analyzed for presence of Vi antibody for chronic typhoid carrier state and bile acid analysis was done in 10 patients in each group.

Results: 116 (30%) patients had culture positive bile. Significantly higher number of patients with gallbladder carcinoma 40 (65%) had culture positive bile as compared to cholelithiasis 52 (42%) and control 24 (12%). Vi Antibodies suggestive of chronic typhoid carrier state were found to be significantly higher in the gallbladder carcinoma group 20 (31%) as compared to controls 22 (11%) (OR 3.596, p < 0.05) however, the difference was statistically insignificant in the cholelithiasis group 12 (11%) (OR 0.859, p > 0.05). There was a 6.84 times higher risk of developing gallbladder carcinoma in culture positive cholelithiasis patients and 5.14 times if both Vi antibody and cultures were positive. Bile analysis showed primary bile acids cholic acid and chenodeoxycholic acid to be lower while secondary bile acids deoxycholic acid and lithocholic acid to be more in the gallbladder carcinoma group (7.268 mg/mL, 9.183 mg/ mL, 14.468 mg/mL, 3.312 mg/mL respectively) than cholelithiasis (17.50 mg/mL, 13.80 mg/mL, 6.07 mg/ mL, 2.05 mg/mL) and control group (19.85 mg/mL, 16.53 mg/mL, 2.71 mg/mL, 1.128 mg/mL respectively). The difference was statistically significant.

Conclusions: Chronic bacterial infection of bile leading to production of carcinogenic precursors might be one of the etiological factors in the pathogenesis of gallbladder carcinoma and hence a target for its prevention.